Gray matter volume alteration is associated with insistence on sameness and cognitive flexibility in autistic youth.

Restricted and repetitive behaviors (RRBs) are hallmark characteristics of autism spectrum disorder (ASD). Previous studies suggest that insistence on sameness (IS) characterized as higher-order RRBs may be a promising subgrouping variable for ASD. Cognitive inflexibility may underpin IS behaviors. However, the neuroanatomical correlates of IS and associated cognitive functions remain unclear. We analyzed data from 140 autistic youth and 124 typically developing (TD) youth (mean age = 15.8 years). Autistic youth were stratified by median-split based on three current IS items in the autism diagnostic interview-revised into two groups (high, HIS, n = 70, and low, LIS, n = 70). Differences in cognitive flexibility were assessed by the Cambridge neuropsychological test automated battery (CANTAB). T1-weighted brain structural images were analyzed using voxel-based morphometry (VBM) to identify differences in gray matter (GM) volume among the three groups. GM volume of regions showing group differences was then correlated with cognitive flexibility. The HIS group showed decreased GM volumes in the left supramarginal gyrus compared to the LIS group and increased GM volumes in the vermis VIII and left cerebellar lobule VIII compared to TD individuals. We did not find significant correlations between regional GM volumes and extra-dimensional shift errors. IS may be a unique RRB component and a potentially valuable stratifier of ASD. However, the neurocognitive underpinnings require further clarification. LAY SUMMARY: The present study found parietal, temporal and cerebellar gray matter volume alterations in autistic youth with greater insistence on sameness. The findings suggest that insistence on sameness may be a useful feature to parse the heterogeneity of the autism spectrum yet further research investigating the underlying neurocognitive mechanism is warranted.